Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
Common adverse reactions reported with netupitant/palonosetron capsules were headache (3.6%), constipation (3.0%) and fatigue (1.2%).

Tabulated list of adverse reactions

Adverse reactions are listed below by MedDRA body system organ class and frequency.
The following convention has been used for classification of frequency: Very common (≥1/10),
Common (≥1/100 to <1/10),
Uncommon (≥1/1,000 to <1/100),
Rare (≥1/10,000 to <1/1,000),
Very rare (<1/10,000),
Not known (cannot be estimated from the available data).


Table1: Adverse reactions
System organ class     Common          Uncommon                 Rare
Infections and                                                  Cystitis infestations
Blood and lymphatic                    Neutropenia              Leukopenia system disorders                       Leucocytosis             Lymphocytosis Metabolism and                         Decreased appetite       Hypokalaemia nutrition disorders
Psychiatric disorders                  Insomnia                 Acute psychosis Mood altered
Sleep disorder
Nervous system          Headache       Dizziness                Hypoaesthesia disorders                                                       Somnolence Eye disorders                                                   Conjunctivitis Vision blurred
Ear and labyrinth                      Vertigo                  Tinnitus disorders
Cardiac disorders                      Atrioventricular block   Arrhythmia first degree
Cardiomyopathy           Atrioventricular block second degree
Conduction disorder      Bundle branch block left
Tachycardia              Bundle branch block right
Mitral valve incompetence
Myocardial ischaemia
Ventricular extrasystoles
Vascular disorders                     Hypertension             Flushing Hypotension
Respiratory, thoracic                  Hiccups and mediastinal disorders
Gastrointestinal        Constipation   Abdominal distension     Dry mouth disorders                              Abdominal pain           Dysphagia Diarrhoea                Eructation
Dyspepsia                Haemorrhoids
Flatulence               Tongue coated
Nausea                   Vomiting
Skin and subcutaneous                  Alopecia                 Erythema tissue disorders                       Urticaria                Pruritus Rash
Musculoskeletal and                                             Back pain connective tissue                                               Pain in extremities disorders
General disorders and   Fatigue        Asthenia                 Feeling hot administration site                                             Non-cardiac chest pain conditions                                                      Product taste abnormal Investigations                         Liver transaminases      Blood bilirubin increased increased
Blood alkaline            Blood creatine phosphokinase phosphatase increased    increased
Blood creatinine          Blood creatine phosphokinase MB increased                increased
Electrocardiogram QT      Blood urea increased prolonged
Electrocardiogram ST segment depression
Electrocardiogram ST-T segment abnormal
Myoglobin blood increased
Neutrophil count increased
Troponin increased

Post-marketing data indicates that the adverse reactions profile is generally similar to that seen in clinical trials.

Description of selected adverse reactions
Netupitant:
No common adverse reactions are attributable to netupitant, the new component of the fixed combination.

Palonosetron:
Cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 0.75 mg.

In addition, eye swelling, dyspnoea and myalgia as adverse reactions have been reported with oral palonosetron but not observed during the development of this medicinal product. All these reactions were uncommon.

Very rare cases of anaphylaxis, anaphylactic/anaphylactoid reactions and shock have been reported from the post-marketing use of intravenous palonosetron. The signs may include hives, itch, angioedema, low blood pressure, throat tightness, chest tightness, dyspnoea, loss of consciousness.

There have also been reports of serotonin syndrome. The signs may include tremor, agitation, sweating, myoclonic movements, hypertonia and fever.

Netupitant and Palonosetron Combinate Capsule:

This medicinal product may contain a trace of lecithin derived from soya. Therefore, patients with known hypersensitivity to peanut or soya should be monitored closely for signs of an allergic reaction.
The signs may include hives, skin rash, itching, difficulty breathing or swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop-in blood pressure.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/